The major purpose of this project is to investigate various parameters of the structure and metabolism of collagen for possible alterations in interstitial fibrosis of lung in humans as compared with normal. Initially, emphasis will be concentrated on idiopathic interstitial fibrosis and pulmonary scleroderma, but as the investigations progress, attention will also be focused on pulmonary sarcoidosis, postradiation fibrosis of lung, pulmonary fibrosis associated with other diffuse connective tissue diseases and other diffuse pulmonary fibrotic disorders. Normal and various diseased lung specimens obtained at autopsy will be used to study the content and types of collagen distributed in various parts of lung. After isolation and purification, collagen, the constituent alpha chains and the CNBr peptides prepared from them will be examined for their molecular weight, and amino acid and carbohydrate composition. The content of various crosslinks will also be carefully quantitated. In addition, viable lung explants obtained by biopsy, or during surgery will be used to study various aspects of the metabolism of collagen in tissue culture. The parameters to be studied include the rate and types of collagen synthesized, the activities of prolyl and lysyl hydroxylases, lysyl oxidase, glycosyltransferases, and specific collagenase. Underlying this proposal is the premise that connective tissues do not simply play a passive role of providing a mechanical lattice, but also participate actively in various physiologic and pathologic processes of the organ, and that therefore definitive information on the behavior of its major element, collagen, will be essential in our understanding of the mechanisms involved in the disease process. Despite the enormous progress achieved in studies of other connective tissues in recent years, little is known about the structure and metabolism of collagen in human lung. We believe the foundation for the approach proposed, carefully laid by us and others during the past several years, is now sufficient to warrant a direct examination of human materials.